P1454: REAL-WORLD OUTCOMES OF BREXUCABTAGENE AUTOLEUCEL (BREXU-CEL) FOR THE TREATMENT OF RELAPSED OR REFRACTORY (R/R) MANTLE CELL LYMPHOMA (MCL) IN THE UNITED STATES (US)
Authors: F. Locke, Z.-H. Hu, J. Gerson, M. J. Frank, L. E. Budde, M. Wang, B. Logan, I. Kloos, R. Siddiqi, J. Shah, H. Xu, M. Pasquini
Journal: HemaSphere (2022)

Background: Brexucabtagene autoleucel (brexu-cel) is a CD19 CAR T-cell therapy approved in the US for adult patients (pts) with r/r MCL. In the primary analysis of the pivotal ZUMA-2 trial, 93% of the pts receiving brexu-cel achieved objective response with a 67% CR rate. Estimated 1-year OS and PFS were 83% and 61% respectively. Grade ≥ 3 CRS and neurologic events occurred in 15% and 31% of the pts. A post-authorization safety study (PASS) for brexu-cel is ongoing in the US using the Center for International Blood and Marrow Transplant Research (CIBMTR) data registry to collect long-term safety and efficacy information for up to 15 years. Aims: We present the first report on real-world outcomes of pts in the PASS receiving commercial brexu-cel for r/r MCL, including pts with no prior exposure to BTK inhibitors (BTKi-naïve) who would otherwise be ineligible for inclusion in the reported ZUMA-2 cohort. Methods: From July 2020 to December 2021, 254 pts (planned total 500 pts) with r/r MCL have been enrolled in the PASS from 70 US centers. Of these, 135 pts had at least one scheduled follow-up at Day 100 and were included in this analysis. Median follow-up was 6 mo. Efficacy outcomes of interest were ORR and CR as best response, DOR, PFS and OS. Adverse events included CRS (Lee 2014 criteria for comparison with ZUMA-2), ICANS (ASTCT consensus grade), prolonged cytopenia, infection and subsequent neoplasm. ORR and CR were evaluated among pts with PET/CT or CT scan assessment. Percentages and 95% Clopper-Pearson exact CIs were calculated for dichotomous outcomes. DOR, PFS and OS were estimated using the Kaplan-Meier estimator. Cumulative incidence functions were used for CRS and ICANS resolution rates. Results: Of the 135 pts, 53% were 65 years or older (median 65.6 years), 79% were male, 87% had an ECOG performance score of 0 or 1, and 61% were chemo-resistant prior to infusion. Extranodal CNS involvement prior to infusion occurred in 5 (4%) pts while clinically significant comorbidities (Sorror 2013) were present in 71% of the pts. Prior to leukapheresis, pts received a median of 4 lines of prior therapy (range 2-12) and 30% had an ASCT. Median time from leukapheresis to infusion was 28 days (range 18-96). Bridging therapy was given to 19% of the pts. Of all, 12 (9%) pts were BTKi-naïve vs 120 (89%) BTKi-exposed. Overall response rate for all pts and pts with ≥ 180 days of follow-up were 84% (95% CI 77-90%) [CR 71% (95% CI 63-79%)] and 78% (95% CI 67-87%) [CR 68% (95% CI 56-78%)], respectively. Of those who achieved CR/PR, 85% (95% CI 75-92%) remained in response at 3 mo. OS and PFS at 6 mo were 79% (95% CI 71-86%) and 66% (95% CI 56-75%), respectively. Grade ≥ 3 CRS and ICANS occurred in 9% (95% CI 5-15%) and 29% (95% CI 22-38%) of the pts. Median time to onset of any grade CRS and ICANS were 4 and 7 days, respectively. Tocilizumab and corticosteroids were given to 92% and 86% of pts with both CRS and ICANS. Most CRS [95% (95% CI 88-98%)] and ICANS [75% (95% CI 63-83%)] resolved by 21 days since onset. For pts who survived Day 30, 22% experienced prolonged cytopenia. Infections requiring treatment occurred in 32% of the pts (20% bacterial, 7% fungal and 17% viral). A total of 4 (3%) pts developed subsequent neoplasms (1 MDS/MPN + squamous cell carcinoma, 1 genitourinary cancer and 2 sarcoma). Image:Summary/Conclusion: Despite short follow-up, this is the largest report on brexu-cel use in the real-world setting. Early results demonstrated consistent safety and efficacy profile of brexu-cel as observed in ZUMA-2 in a population with broader demographics, disease and treatment profile.